Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P19971 (TYPH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 171. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Thymidine phosphorylase

Short name=TP
EC=2.4.2.4
Alternative name(s):
Gliostatin
Platelet-derived endothelial cell growth factor
Short name=PD-ECGF
TdRPase
Gene names
Name:TYMP
Synonyms:ECGF1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length482 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May have a role in maintaining the integrity of the blood vessels. Has growth promoting activity on endothelial cells, angiogenic activity in vivo and chemotactic activity on endothelial cells in vitro. Ref.8

Catalyzes the reversible phosphorolysis of thymidine. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis. Ref.8

Catalytic activity

Thymidine + phosphate = thymine + 2-deoxy-alpha-D-ribose 1-phosphate.

Pathway

Pyrimidine metabolism; dTMP biosynthesis via salvage pathway; dTMP from thymine: step 1/2.

Subunit structure

Homodimer. Ref.10 Ref.11

Involvement in disease

Mitochondrial DNA depletion syndrome 1, MNGIE type (MTDPS1) [MIM:603041]: A multisystem disease associated with mitochondrial dysfunction. It is clinically characterized by onset between the second and fifth decades of life, ptosis, progressive external ophthalmoplegia, gastrointestinal dysmotility (often pseudoobstruction), diffuse leukoencephalopathy, cachexia, peripheral neuropathy, and myopathy.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13 Ref.14

Sequence similarities

Belongs to the thymidine/pyrimidine-nucleoside phosphorylase family.

Ontologies

Keywords
   Biological processAngiogenesis
Chemotaxis
Differentiation
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Progressive external ophthalmoplegia
   DomainRepeat
   Molecular functionDevelopmental protein
Glycosyltransferase
Growth factor
Transferase
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processDNA replication

Traceable author statement Ref.13. Source: ProtInc

angiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

cell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

chemotaxis

Inferred from electronic annotation. Source: UniProtKB-KW

mitochondrial genome maintenance

Traceable author statement Ref.13. Source: ProtInc

nucleobase-containing small molecule metabolic process

Traceable author statement. Source: Reactome

pyrimidine nucleobase metabolic process

Traceable author statement. Source: Reactome

pyrimidine nucleoside catabolic process

Traceable author statement. Source: Reactome

pyrimidine nucleoside salvage

Traceable author statement. Source: Reactome

pyrimidine nucleotide metabolic process

Traceable author statement Ref.13. Source: ProtInc

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

   Molecular_functionphosphorylase activity

Inferred from electronic annotation. Source: InterPro

platelet-derived growth factor receptor binding

Traceable author statement PubMed 2005900. Source: ProtInc

pyrimidine-nucleoside phosphorylase activity

Inferred from electronic annotation. Source: InterPro

thymidine phosphorylase activity

Traceable author statement Ref.13. Source: ProtInc

transferase activity, transferring pentosyl groups

Inferred from experiment. Source: Reactome

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P19971-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P19971-2)

The sequence of this isoform differs from the canonical sequence as follows:
     386-386: D → DAPLPA
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Propeptide1 – 1010
PRO_0000035874
Chain11 – 482472Thymidine phosphorylase
PRO_0000035875

Regions

Repeat265 – 27915R-V-A-A-A-L-X(5,6)-L-G-R
Repeat329 – 34214R-V-A-A-A-L-X(5,6)-L-G-R
Repeat393 – 4019R-A-L-X-X-A-L-V-L
Repeat453 – 4619R-A-L-X-X-A-L-V-L

Sites

Binding site1161Substrate
Binding site2021Substrate
Binding site2171Substrate
Binding site2211Substrate

Natural variations

Alternative sequence3861D → DAPLPA in isoform 2.
VSP_045556
Natural variant441R → Q in MTDPS1. Ref.14
VAR_016777
Natural variant1451G → R in MTDPS1. Ref.13
VAR_007643
Natural variant1531G → S in MTDPS1. Ref.13
VAR_007644
Natural variant2221K → R in MTDPS1. Ref.13
VAR_007645
Natural variant2891E → A in MTDPS1. Ref.13
VAR_007646
Natural variant397 – 3982Missing in MTDPS1.
VAR_007647
Natural variant4711S → L. Ref.1 Ref.5
Corresponds to variant rs11479 [ dbSNP | Ensembl ].
VAR_007648

Experimental info

Mutagenesis1991Y → A: Abolishes catalytic activity. Ref.12
Mutagenesis1991Y → F: Reduced catalytic activity. Ref.12
Mutagenesis1991Y → L: Reduced catalytic activity. Ref.12
Sequence conflict1951D → E in AAH18160. Ref.5

Secondary structure

................................................................. 482
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 7, 2005. Version 2.
Checksum: 0652FA0B8F3BDE28

FASTA48249,955
        10         20         30         40         50         60 
MAALMTPGTG APPAPGDFSG EGSQGLPDPS PEPKQLPELI RMKRDGGRLS EADIRGFVAA 

        70         80         90        100        110        120 
VVNGSAQGAQ IGAMLMAIRL RGMDLEETSV LTQALAQSGQ QLEWPEAWRQ QLVDKHSTGG 

       130        140        150        160        170        180 
VGDKVSLVLA PALAACGCKV PMISGRGLGH TGGTLDKLES IPGFNVIQSP EQMQVLLDQA 

       190        200        210        220        230        240 
GCCIVGQSEQ LVPADGILYA ARDVTATVDS LPLITASILS KKLVEGLSAL VVDVKFGGAA 

       250        260        270        280        290        300 
VFPNQEQARE LAKTLVGVGA SLGLRVAAAL TAMDKPLGRC VGHALEVEEA LLCMDGAGPP 

       310        320        330        340        350        360 
DLRDLVTTLG GALLWLSGHA GTQAQGAARV AAALDDGSAL GRFERMLAAQ GVDPGLARAL 

       370        380        390        400        410        420 
CSGSPAERRQ LLPRAREQEE LLAPADGTVE LVRALPLALV LHELGAGRSR AGEPLRLGVG 

       430        440        450        460        470        480 
AELLVDVGQR LRRGTPWLRV HRDGPALSGP QSRALQEALV LSDRAPFAAP SPFAELVLPP 


QQ 

« Hide

Isoform 2 [UniParc].

Checksum: C2F16246C51DCE00
Show »

FASTA48750,405

References

« Hide 'large scale' references
[1]"Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor."
Ishikawa F., Miyazono K., Hellman U., Drexler H., Wernstedt C., Hagiwara K., Usuki K., Takaku F., Risau W., Heldin C.-H.
Nature 338:557-562(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, VARIANT LEU-471.
Tissue: Placenta.
[2]"Expression of recombinant platelet-derived endothelial cell growth factor in the yeast Saccharomyces cerevisiae."
Finnis C., Goodey A., Courtney M., Sleep D.
Yeast 8:57-60(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Dermoid cancer.
[4]"The DNA sequence of human chromosome 22."
Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. expand/collapse author list , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H.
Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT LEU-471.
Tissue: Brain and Lung.
[6]"Angiogenic factor."
Furukawa T., Yoshimura A., Sumizawa T., Haraguchi M., Akiyama S., Fukui K., Yamada Y.
Nature 356:668-668(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE OF 149-244, PROTEIN SEQUENCE OF 125-178 AND 236-244.
[7]"Neurotrophic action of gliostatin on cortical neurons. Identity of gliostatin and platelet-derived endothelial cell growth factor."
Asai K., Nakanishi K., Isobe I., Eksioglu Y.Z., Hirano A., Hama K., Miyamoto T., Kato T.
J. Biol. Chem. 267:20311-20316(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE.
[8]"Platelet-derived endothelial cell growth factor has thymidine phosphorylase activity."
Usuki K., Saras J., Waltenberger J., Miyazono K., Pierce G., Thomason A., Heldin C.-H.
Biochem. Biophys. Res. Commun. 184:1311-1316(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Crystal structure of human thymidine phosphorylase in complex with a small molecule inhibitor."
Norman R.A., Barry S.T., Bate M., Breed J., Colls J.G., Ernill R.J., Luke R.W., Minshull C.A., McAlister M.S., McCall E.J., McMiken H.H., Paterson D.S., Timms D., Tucker J.A., Pauptit R.A.
Structure 12:75-84(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.11 ANGSTROMS) OF 12-482 IN COMPLEX WITH INHIBITOR, SUBUNIT.
[11]"Structural basis for non-competitive product inhibition in human thymidine phosphorylase: implications for drug design."
El Omari K., Bronckaers A., Liekens S., Perez-Perez M.J., Balzarini J., Stammers D.K.
Biochem. J. 399:199-204(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.31 ANGSTROMS), SUBUNIT.
[12]"Structures of native human thymidine phosphorylase and in complex with 5-iodouracil."
Mitsiki E., Papageorgiou A.C., Iyer S., Thiyagarajan N., Prior S.H., Sleep D., Finnis C., Acharya K.R.
Biochem. Biophys. Res. Commun. 386:666-670(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) ALONE AND IN COMPLEX WITH 5-IODOURACIL, SUBSTRATE-BINDING SITES, MUTAGENESIS OF TYR-199.
[13]"Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder."
Nishino I., Spinazzola A., Hirano M.
Science 283:689-692(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MTDPS1 ARG-145; SER-153; ARG-222; ALA-289 AND 397-LEU-ALA-398 DEL.
[14]"Phenotypic variability in a Spanish family with MNGIE."
Gamez J., Ferreiro C., Accarino M.L., Guarner L., Tadesse S., Marti R.A., Andreu A.L., Raguer N., Cervera C., Hirano M.
Neurology 59:455-457(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MTDPS1 GLN-44.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M63193 mRNA. Translation: AAA60043.1.
AK225269 mRNA. No translation available.
U62317 Genomic DNA. Translation: AAB03344.2.
BC018160 mRNA. Translation: AAH18160.1.
BC052211 mRNA. Translation: AAH52211.1.
CCDSCCDS14096.1. [P19971-1]
CCDS58811.1. [P19971-2]
PIRS03904.
RefSeqNP_001107227.1. NM_001113755.2. [P19971-1]
NP_001107228.1. NM_001113756.2. [P19971-1]
NP_001244917.1. NM_001257988.1. [P19971-1]
NP_001244918.1. NM_001257989.1. [P19971-2]
NP_001944.1. NM_001953.4. [P19971-1]
UniGeneHs.180903.
Hs.730607.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1UOUX-ray2.11A12-482[»]
2J0FX-ray2.31A/B/C/D1-482[»]
2WK5X-ray2.99A/B/C/D1-482[»]
2WK6X-ray2.50A/B1-482[»]
ProteinModelPortalP19971.
SMRP19971. Positions 32-479.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108219. 8 interactions.
IntActP19971. 1 interaction.
STRING9606.ENSP00000252029.

Chemistry

BindingDBP19971.
ChEMBLCHEMBL3106.
DrugBankDB01101. Capecitabine.
DB01248. Docetaxel.
DB00322. Floxuridine.
DB00544. Fluorouracil.
DB00795. Sulfasalazine.
DB00675. Tamoxifen.

PTM databases

PhosphoSiteP19971.

Polymorphism databases

DMDM67477361.

2D gel databases

OGPP19971.

Proteomic databases

MaxQBP19971.
PaxDbP19971.
PRIDEP19971.

Protocols and materials databases

DNASU1890.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000252029; ENSP00000252029; ENSG00000025708. [P19971-1]
ENST00000395678; ENSP00000379036; ENSG00000025708. [P19971-1]
ENST00000395680; ENSP00000379037; ENSG00000025708. [P19971-1]
ENST00000395681; ENSP00000379038; ENSG00000025708. [P19971-2]
GeneID1890.
KEGGhsa:1890.
UCSCuc003bmb.5. human. [P19971-1]

Organism-specific databases

CTD1890.
GeneCardsGC22M050964.
GeneReviewsTYMP.
HGNCHGNC:3148. TYMP.
HPACAB002518.
HPA001072.
MIM131222. gene.
603041. phenotype.
neXtProtNX_P19971.
Orphanet298. Mitochondrial neurogastrointestinal encephalomyopathy.
PharmGKBPA162407502.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0213.
HOGENOMHOG000047313.
HOVERGENHBG000082.
KOK00758.
OMANVGHTLE.
OrthoDBEOG744T97.
PhylomeDBP19971.
TreeFamTF332198.

Enzyme and pathway databases

BioCycMetaCyc:HS00442-MONOMER.
BRENDA2.4.2.4. 2681.
ReactomeREACT_111217. Metabolism.
SABIO-RKP19971.
UniPathwayUPA00578; UER00638.

Gene expression databases

ArrayExpressP19971.
BgeeP19971.
CleanExHS_TYMP.
GenevestigatorP19971.

Family and domain databases

Gene3D3.40.1030.10. 1 hit.
3.90.1170.30. 1 hit.
InterProIPR000312. Glycosyl_Trfase_fam3.
IPR017459. Glycosyl_Trfase_fam3_N_dom.
IPR013102. PYNP_C.
IPR018090. Pyrmidine_PPas_bac/euk.
IPR000053. Pyrmidine_PPase.
IPR017872. Pyrmidine_PPase_CS.
[Graphical view]
PANTHERPTHR10515. PTHR10515. 1 hit.
PfamPF02885. Glycos_trans_3N. 1 hit.
PF00591. Glycos_transf_3. 1 hit.
PF07831. PYNP_C. 1 hit.
[Graphical view]
PIRSFPIRSF000478. TP_PyNP. 1 hit.
SMARTSM00941. PYNP_C. 1 hit.
[Graphical view]
SUPFAMSSF47648. SSF47648. 1 hit.
SSF52418. SSF52418. 1 hit.
SSF54680. SSF54680. 1 hit.
TIGRFAMsTIGR02644. Y_phosphoryl. 1 hit.
PROSITEPS00647. THYMID_PHOSPHORYLASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP19971.
GeneWikiECGF1.
GenomeRNAi1890.
NextBio7707.
PROP19971.
SOURCESearch...

Entry information

Entry nameTYPH_HUMAN
AccessionPrimary (citable) accession number: P19971
Secondary accession number(s): A8MW15 expand/collapse secondary AC list , H9KVA0, Q13390, Q8WVB7
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: June 7, 2005
Last modified: July 9, 2014
This is version 171 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 22

Human chromosome 22: entries, gene names and cross-references to MIM